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Acta Neurochirurgica May 2024To identify differences in the presentation and surgical outcomes between very large (30-39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared...
PURPOSE
To identify differences in the presentation and surgical outcomes between very large (30-39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared to the smaller group (< 30 mm) (non-LARGE group).
METHODS
Eighty patients with very large (n = 44) or giant (n = 36) PAs and 226 patients in the non-LARGE group who underwent tumor resection by pituitary surgery between 2008 and 2023 were studied. Hormonal, radiological, ophthalmological, and pathological data, and surgical outcomes were evaluated.
RESULTS
Preoperatively, patients of the LARGE group presented more frequently with visual impairment (82.5% vs. 22.1%, P < 0.001) and with pituitary apoplexy (15.0% vs. 2.7%, P < 0.001) than the non-LARGE group. Moreover, the LARGE group were more commonly associated with preoperative panhypopituitarism (28.8% vs. 6.2%, P < 0.001). This group presented cavernous sinus invasion more frequently (71.3% vs. 23.9%, P < 0.001). The non-LARGE group achieved surgical cure more often than the LARGE group (79.7% vs. 50.0%, P < 0.001), and the rate of major complications was higher in the latest (8.8% vs. 1.3%, P < 0.004).
CONCLUSIONS
PAs ≥ 30 mm are most frequently accompanied by hormonal dysfunction, cavernous sinus invasion, and visual impairment. All this implies lower resection rates and higher postoperative complications than the smaller adenomas, posing a real surgical challenge.
Topics: Humans; Pituitary Neoplasms; Adenoma; Male; Female; Middle Aged; Adult; Treatment Outcome; Aged; Cohort Studies; Vision Disorders; Postoperative Complications; Hypopituitarism; Retrospective Studies; Tumor Burden
PubMed: 38772927
DOI: 10.1007/s00701-024-06107-w -
European Journal of Endocrinology Jun 2024The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary...
OBJECTIVE
The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA).
DESIGN
This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment.
METHODS
Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality.
RESULTS
Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline.
CONCLUSION
In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.
Topics: Humans; Acromegaly; Female; Male; Middle Aged; Retrospective Studies; Adult; Cabergoline; Treatment Outcome; Prolactin; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Adenoma; Aged; Drug Therapy, Combination; Somatostatin; Pituitary Neoplasms; Spain
PubMed: 38771697
DOI: 10.1093/ejendo/lvae053 -
Clinical and Translational Medicine May 2024The three-dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within...
BACKGROUND
The three-dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored.
METHODS
We employed Hi-C and RNA-seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns.
RESULTS
We observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi-C and RNA-seq data demonstrated that changes inhigher-order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/β-Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT-PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro.
CONCLUSION
Our results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.
Topics: Humans; Chromatin; Pituitary Neoplasms; Somatotrophs
PubMed: 38769659
DOI: 10.1002/ctm2.1682 -
La Clinica Terapeutica 2024We assessed the value of histogram analysis (HA) of apparent diffusion coefficient (ADC) maps for grading low-grade (LGG) and high-grade (HGG) gliomas. (Comparative Study)
Comparative Study Observational Study
OBJECTIVES
We assessed the value of histogram analysis (HA) of apparent diffusion coefficient (ADC) maps for grading low-grade (LGG) and high-grade (HGG) gliomas.
METHODS
We compared the diagnostic performance of two region-of-interest (ROI) placement methods (ROI 1: the entire tumor; ROI 2: the tumor excluding cystic and necrotic portions). We retrospectively evaluated 54 patients with supratentorial gliomas (18 LGG and 36 HGG). All subjects underwent standard 3T contrast-enhanced magnetic resonance imaging. Histogram parameters of ADC maps calculated with the two segmentation methods comprised mean, median, maxi-mum, minimum, kurtosis, skewness, entropy, standard deviation (sd), mean of positive pixels (mpp), uniformity of positive pixels, and their ratios (r) between lesion and normal white matter. They were compared using the independent t-test, chi-square test, or Mann-Whitney U test. For statistically significant results, receiver operating characteristic curves were constructed, and the optimal cutoff value, sensitivity, and specificity were determined by maximizing Youden's index.
RESULTS
The ROI 1 method resulted in significantly higher rADC mean, rADC median, and rADC mpp for LGG than for HGG; these parameters had value for predicting the histological glioma grade with a cutoff (sensitivity, specificity) of 1.88 (77.8%, 61.1%), 2.25 (44.4%, 97.2%), and 1.88 (77.8%, 63.9%), respectively. The ROI 2 method resulted in significantly higher ADC mean, ADC median, ADC mpp, ADC sd, ADC max, rADC median, rADC mpp, rADC mean, rADC sd, and rADC max for LGG than for HGG, while skewness was lower for LGG than for HGG (0.27 [0.98] vs 0.91 [0.81], p = 0.014). In ROI 2, ADC median, ADC mpp, ADC mean, rADC median, rADC mpp, and rADC mean performed well in differentiating glioma grade with cutoffs (sensitivity, specificity) of 1.28 (77.8%, 88.9%), 1.28 (77.8%, 88.9%), 1.25 (77.8%, 91.7%), 1.81 (83.3%, 91.7%), 1.74 (83.3%, 91.7%), and 1.81 (83.3%, 91.7%), respectively.
CONCLUSIONS
HA parameters had value for grading gliomas. Ex-cluding cystic and necrotic portions of the tumor for measuring HA parameters was preferable to using the entire tumor as the ROI. In this segmentation, rADC median showed the highest performance in predicting histological glioma grade, followed by rADC mpp, rADC mean, ADC median, ADC mpp, and ADC mean.
Topics: Humans; Glioma; Female; Middle Aged; Retrospective Studies; Male; Neoplasm Grading; Adult; Diffusion Magnetic Resonance Imaging; Brain Neoplasms; Aged; Young Adult
PubMed: 38767069
DOI: 10.7417/CT.2024.5053 -
Journal of Surgical Case Reports May 2024Primary intracranial melanocytoma is an uncommon benign pigmented tumor arising from leptomeningeal melanocytes. Neuroimaging characteristics of central nervous system...
Primary intracranial melanocytoma is an uncommon benign pigmented tumor arising from leptomeningeal melanocytes. Neuroimaging characteristics of central nervous system melanocytoma are distinct from similarly presenting intracranial neoplasms and can aid in diagnosis prior to histopathological examination. In rare cases, there may be more than one lesion present. We report a case of a 19-year-old woman presenting with progressively worsening headaches, nausea, emesis, and generalized weakness of 2 months. Imaging revealed tumors in the parietal and ipsilateral medial temporal lobe. The patient underwent gross total resection of the parietal lesion which histopathological assessment revealed to be primary intracranial meningeal melanocytoma. This case highlights the utility of specific imaging criteria such as diffusely increased T1 signal without enhancement in the initial diagnostic evaluation of intracranial melanocytoma. We also describe the clinical characteristics, management strategy, and histopathological features of a rare case of a patient with multiple primary intracranial melanocytoma lesions.
PubMed: 38764735
DOI: 10.1093/jscr/rjae332 -
Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.Journal of Biochemical and Molecular... Jun 2024We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor...
We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.
Topics: MicroRNAs; Curcumin; Humans; Autophagy; Prolactinoma; Cell Line, Tumor; Up-Regulation; Male; TOR Serine-Threonine Kinases; Female; Pituitary Neoplasms; Adult; Proto-Oncogene Proteins c-akt; Antineoplastic Agents; Signal Transduction; Cell Proliferation; Middle Aged; Rats
PubMed: 38764151
DOI: 10.1002/jbt.23734 -
Pituitary Jun 2024The contents of Rathke's cleft cysts (RCCs) vary from clear and slightly viscous to purulent. Surgical treatment of symptomatic RCCs involves removing the cyst contents,...
PURPOSE
The contents of Rathke's cleft cysts (RCCs) vary from clear and slightly viscous to purulent. Surgical treatment of symptomatic RCCs involves removing the cyst contents, whereas additional cyst-wall opening to prevent reaccumulation is at the surgeon's discretion. The macroscopic findings of the cyst content can reflect the nature of RCCs and would aid in surgical method selection.
METHODS
We retrospectively reviewed the records of 42 patients with symptomatic RCCs who underwent transsphenoidal surgery at our institute between January 2010 and March 2022. According to the intraoperative findings, cyst contents were classified into type A (purulent), type B (turbid white with mixed semisolids), or type C (clear and slightly viscous). Clinical and imaging findings and early recurrence rate (within two years) were compared according to the cyst content type.
RESULTS
There were 42 patients classified into three types. Patients with type C were the oldest (65.4 ± 10.4 years), and type A included more females (92.9%). For magnetic resonance imaging, type-A patients showed contrast-enhanced cyst wall (92.9%), type-B patients had intracystic nodules (57.1%), and all type-C patients showed low T1 and high T2 intensities with larger cyst volumes. Fewer asymptomatic patients had type C. Preoperative pituitary dysfunction was most common in type A (71.4%). Early recurrence was observed in types A and C, which were considered candidates for cyst-wall opening.
CONCLUSION
The clinical characteristics and surgical prognosis of RCCs depend on the nature of their contents.
Topics: Humans; Female; Central Nervous System Cysts; Male; Retrospective Studies; Middle Aged; Aged; Magnetic Resonance Imaging; Pituitary Neoplasms; Adult; Neoplasm Recurrence, Local
PubMed: 38761321
DOI: 10.1007/s11102-024-01395-y -
Journal of Neuro-oncology Jun 2024Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very... (Review)
Review
CONTEXT
Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very rare. Despite their benign histological nature (aggressive tumors are rare and malignant ones exceptional), FPAs could cause significant morbidity and increased mortality due to complications associated with hormonal excess syndromes and/or mass effect leading to compression of adjacent structures. This mini review will focus on the increasing role of medical therapy in the multimodal treatment, which also includes transsphenoidal surgery (TSS) and radiotherapy.
EVIDENCE SYNTHESIS
Most patients with prolactinomas are treated only with medications, but surgery could be considered for some patients in a specialized pituitary center, if higher chances of cure. Dopamine agonists, especially cabergoline, are efficient in reducing tumor size and normalizing prolactin. TSS is the first-line treatment for all other FPAs, but most patients require complex adjuvant treatment, including a combination of therapeutic approaches. Medical therapy is the cornerstone of treatment in all patients after unsuccessful surgery or when surgery cannot be offered and includes somatostatin receptor ligands and dopamine agonists (almost all FPAs), growth hormone receptor antagonists (acromegaly), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers (Cushing's disease). Novel medical treatments, especially for acromegaly and Cushing's disease are under research.
CONCLUSIONS
An enlarged panel of effective drugs available with increased knowledge of predictive factors for response and/or adverse effects will enhance the possibility to offer a more individualized treatment. This would not only improve disease control and prognosis, but also quality of life.
Topics: Humans; Pituitary Neoplasms; Adenoma; Combined Modality Therapy; Clinical Trials as Topic
PubMed: 38760632
DOI: 10.1007/s11060-024-04670-x -
Acta Neuropathologica May 2024Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical...
Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.3 × 10 and p = 8.5 × 10, respectively). Within the corticotroph lineage, a characteristic pattern of recurrent chromosomal LOH in 12 specific chromosomes was associated with treatment-refractoriness (occurring in 11 of 14 treatment-refractory versus 1 of 14 benign corticotroph PitNETs, p = 1.7 × 10). Across the cohort, a higher fraction of LOH was identified in tumors with TP53 mutations (p = 3.3 × 10). A machine learning approach identified loss of heterozygosity as the most predictive variable for aggressive, treatment-refractory behavior, outperforming the most common gene-level alteration, TP53, with an accuracy of 0.88 (95% CI: 0.70-0.96). Aggressive, treatment-refractory PitNETs are characterized by significant aneuploidy due to widespread chromosomal LOH, most prominently in the corticotroph tumors. This LOH predicts treatment-refractoriness with high accuracy and represents a novel biomarker for this poorly defined PitNET category.
Topics: Humans; Loss of Heterozygosity; Pituitary Neoplasms; Neuroendocrine Tumors; Male; Female; Middle Aged; Adult; Aged; Retrospective Studies; Mutation; Prospective Studies
PubMed: 38758238
DOI: 10.1007/s00401-024-02736-8 -
Frontiers in Endocrinology 2024The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role...
BACKGROUND
The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).
METHODS
A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.
RESULTS
Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.
CONCLUSION
The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.
Topics: Humans; World Health Organization; Female; Male; Middle Aged; Pituitary Neoplasms; Neuroendocrine Tumors; Adult; Aged; Prognosis; Young Adult; Follow-Up Studies; T-Box Domain Proteins
PubMed: 38756997
DOI: 10.3389/fendo.2024.1368944